Slansky Lab

Research interests:Many factors limit the adaptive immune system from killing tumors; tumors and the resident inflammatory cells have numerous ways of inhibiting productive B and T cell responses. In addition, most antigens on tumors are “self antigens” not “neoantigens” or mutated proteins that lead to tumor development. Therefore immune cells bind weakly to tumors and respond weakly. Poor responses to tumor/self antigens seem detrimental, but actually this protects us from other autoimmune issues. If the immune system could be better stimulated when encountering tumors, they might mediate more effective responses against the tumor. Our goal is to make this happen.

Using an animal model for colon cancer, we are determining what substitutions in tumor antigen peptides improve antitumor immunity. These so-called “mimotope” peptides (mimics of epitopes) activate T cells that respond to the tumor more effectively than the natural tumor antigen. To understand how mimotope peptides affect T cell responses against tumors, we are characterizing the T cells responding to these peptides. Using high throughput sequencing techniques, we now know that T cells that are elicited by effective vaccines have TCRs with similar sequences as those found in the tumor without a vaccine. In this system, we have also started studying the epigenome of tumor-specific T cells that respond to effective vaccines and to the tumor.

We have a collaborative DoD-supported project with the labs of Drs. John Kappler, Peter Lee (City of Hope), and Paul Spellman (OHSU). This multi-team project combines genomics and immunotherapy to develop a new generation of therapeutic breast cancer vaccines, which improve the immune system’s ability to fight breast cancer. We are working on identifying the cognate antigens and mimotopes of breast cancer infiltrating T cells by using the T cells directly out of the tumors.

Finally, two blossoming projects in the lab: 1. We are collaborating with the Director of the Lung Cancer Center at National Jewish Health, Dr. Jeff Kern and a number of thoracic surgeons on the immune cells in human lung cancer. We are dissecting the function and the targets of B cells in the tumor verses tumor-adjacent lung tissue. Like the DoD project above, we hope to identify antigens that, if included in therapeutic vaccines, would eventually improve the survival of lung cancer patients. 2. Using animal and human models for bladder cancer, we are working with Drs. Tom Flaig, Xiaoping Yang, Shandra Wilson, and Dan Theodorescu of the UCCC to identify markers and mechanisms of non-invasive bladder cancer that fails BCG treatment.

Success of these studies may have direct implications for the design and development of tumor vaccines.